It is known that PCP induces mental symptoms which resemble closely to various symptoms of schizophrenia, including negative symptoms [Am. J. Psychiat., 135, 1081 (1987); Am. J. Psychiat., 148, 1301 (1991)]. On the other hand, various types of abnormal behavior are induced when PCP is administered to animals. Accordingly, it is considered that a drug which specifically inhibits the PCP-induced abnormal behavior of animals (anti-PCP action) are useful as an agent for the treatment of schizophrenia in humans [Shinkei Seishin Yakuri (nervous and mental pharmacology), 15 (10), 651 (1993); Behav. Brain Res., 74, 45 (1996)]. In addition, since PCP has an NMDA receptor inhibition action [J. Pharm. Exp. Thera., 238, 938 (1986); Br. J. Pharmacol., 79, 565 (1982)], it is considered that such agents having anti-PCP actions are also useful as agents for the treatment of diseases caused by the reduction of NMDA receptor functions, namely disturbance of memory or cognition, delirium or the like problematic behavior in senile dementia [J. Neurochem., 54 (2), 526 (1990); Life Science, 55 (25/26), 2147 (1994)].
Dopamine receptor blockers have hitherto been used mainly as agents for the treatment of schizophrenia. However, these dopamine blockers have problems in that they show less effects for negative symptoms and generate extrapyramidal symptoms and the like side effects [T. I. P. S., 13, 116 (1992)].
On the contrary, specific anti-PCP agents are excellent in terms of the facts that they can improve negative symptoms of schizophrenia, for which dopamine blockers are not effective, and do not cause the side effects like the case of dopamine blockers.
Previously, the inventors of the present invention have found that a novel thiophene derivative having a nitrogen-containing cycloalkyl lower alkyl group has an anti-PCP action and have reported the results in WO 94/225450 or WO 95/22910.
On the other hand, JP-A-62-192379 discloses a compound represented by the following general formula ##STR2## (see this published application for detailed definitions), which will become a thiophene derivative having a nitrogen-containing cycloalkyl group and a thiazole group, depending on the selection of substituents. Similar compounds are also described in JP-A-61-18178. According to the descriptions in both of these published applications, these compounds have anti-hypoxic action, anti-amnestic action and anti-anxiety action and are useful also as antidementia agents or anxiolytic agents. However, they do not disclose about anti-PCP actions.
In addition, Journal of the Chemical Society, Perkin Transactions Pt.1: Organic Chemistry, 22, 2355 (1976) describes a method for the synthesis of a compound represented by the following general formula ##STR3## (see the literature for detailed definitions), but it also does not suggest or disclose about anti-PCP actions.
The novel thiophene derivative of the present invention represented by the general formula (I) excludes the compounds described in the aforementioned Japanese published applications and literature and is clearly different from the compound disclosed by the present inventors in the aforementioned international publication pamphlet in terms of their structures.